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Clinical Laboratories and Pathology Groups

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Clinical Laboratories and Pathology Groups

Hosted by Robert Michel
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There’s evidence that a cancer drug can cut deaths from lung cancer by as much as 50% when pathology testing indicates the patient has the EGFR mutation

Results from a decade-long clinical trial indicate that lung cancer patients with the epidermal growth factor receptor (EGFR) mutation have significantly better survival rates when treated with the drug osimertinib. This is a positive step forward for precision medicine and will give clinical laboratories an opportunity to deliver more value to physicians and patients.

The study known as ADAURA was led by scientists at Yale University and funded by British pharmaceutical/biotechnology company AstraZeneca. The researchers recently found that taking the cancer drug osimertinib (brand name Tagrisso) reduces by half the number of deaths among patients who had undergone surgery for EGFR–mutated, stage IB to IIIA non-small-cell lung cancer (NSCLC), according to NBC News.

Lung cancer has been one of the toughest types of cancers to diagnose early. When finally diagnosed, many patients do not have a good prognosis. Thus, the results of this multi-national study—and the connection involving patients with the EGFR gene—is a welcome development that promises better outcomes for cancer patients.

At the same time, this increases the value of EGFR as a biomarker for clinical laboratories and pathology groups that offer EGFR testing. It could become a companion diagnostic test—part of a clinical guideline for diagnosing lung cancer—that helps identify appropriate anti-cancer drugs for specific patients.

The researchers published their findings in the New England Journal of Medicine (NEJM) titled, “Overall Survival with Osimertinib in Resected EGFR-Mutated NSCLC.” They also presented the results of their study at the American Society for Clinical Oncology (ASCO) conference.

“Adjuvant osimertinib is currently the only EGFR tyrosine kinase inhibitor to translate a statistically significant and practice-changing disease-free survival benefit into a significant [overall survival] benefit in a phase 3 trial, supporting osimertinib as the standard of care for patients in this setting,” said Roy Herbst, MD, PhD, Deputy Director and Chief of Medical Oncology at Yale Cancer Center, who led the Yale study, at the 2023 ASCO Annual Meeting, according to an ASCO news release. (Photo copyright: Yale School of Medicine.)

Identifying Best Candidates for Specific Cancer Drugs

The results of the Yale-led study of the cancer drug osimertinib suggest that testing for a mutation in the EGFR gene could become part of the standard-of-care for NSCLC. Researchers found that NSCLC patients with the mutation showed improved survival rates and reduced risk of recurrence when taking the drug following surgery. EGFR tests could thus become companion diagnostics to determine whether patients are good candidates for the drug.

“We have been using one-size-fits-all adjuvant chemotherapy for every patient with lung cancer despite a decade of advances in targeted treatments for select groups of patients that result in dramatically better outcomes,” Nathan Pennell, MD, PhD, Vice Chair of Clinical Research and Director, Lung Cancer Medical Oncology Program Cleveland Clinic Taussig Cancer Institute, told the ASCO Post.

Pennell, who was not involved in the Yale research, described the finding as “a first for the lung cancer field,” and said adjuvant osimertinib “should be the new standard of care” for patients with EGFR-mutated NSCLC.

‘Practice-changing’ Cancer Drug

The study was led by Roy S. Herbst, MD, PhD, Deputy Director and Chief of Medical Oncology at Yale Cancer Center and Assistant Dean for Translational Research at Yale School of Medicine. Herbst is the principal investigator for the ADAURA global multi-site clinical trial which enrolled 682 patients with stage IB-IIIA NSCLC, in an effort to determine the efficacy of the cancer drug osimertinib, a pill taken once a day, which, according to NBC News, has fewer major side effects than chemotherapy.

The FDA approved the drug in 2015 for patients with advanced lung cancer. In 2020, the agency approved its use at earlier stages of the disease.

The ADAURA study included patients from 26 countries across Europe, North America, South America, and the Asia-Pacific region. About half of the patients took the pill each day for three years following surgery. The other half received a placebo.

According to a Yale news release, the researchers reported that 88% of patients treated with the drug were still alive five years later, compared with 78% of patients who received the placebo.

Earlier research demonstrated that the drug prevented recurrence of tumors and kept the disease from spreading to other organs, NBC News reported. “However, what we are seeing now is that patients will also live longer,” said oncologist Charu Aggarwal, MD, MPH, of the University of Pennsylvania’s Perelman School of Medicine, who was not involved in the study.

Herbst described the drug as “practice-changing” in the Yale news story.

An EGFR ‘Off Switch’

Non-small cell lung cancer is the most common form of lung cancer, The Guardian reported, adding that the EGFR mutation “is found in about a quarter of global lung cancer cases, and accounts for as many as 40% of cases in Asia. An EGFR mutation is more common in women than men and in people who have never smoked or have been light smokers.”

The mutation can cause cells to “excessively divide and multiply, which may cause cancer,” NBC News explained. Herbst described osimertinib as an “off” switch for the mutation.

“I think we’re curing some patients,” he said at the ASCO annual meeting, NBC News reported. “We’re really showing progress in lung cancer like never before,” he noted, adding that the results were “about twice as good as we expected.

“Overall survival has historically been considered the gold standard efficacy endpoint for randomized adjuvant clinical trials. The results of the ADAURA trial will broaden treatment access for patients with EGFR-mutated NSCLC,” Herbst told ASCO Post. “Together with the practice-changing disease-free survival data from our primary analysis, the overall survival benefit instills confidence that adjuvant osimertinib is the standard of care for patients with resected EGFR-mutated stage IB to IIIA NSCLC.”

Side effects of the pill include skin rashes and mild diarrhea, but in general the drug is “quite well tolerated,” Herbst said.

Impact on Labs

In Herbst’s view, the results of the Yale study demonstrate that patients diagnosed with lung cancer should be tested for the EGFR mutation, which is not always the case, The Guardian reported. “This further reinforces the need to identify these patients with available biomarkers at the time of diagnosis and before treatment begins,” he said.

Aggarwal agreed, telling NBC News that data from the study could be a “call to action” for more EGFR screening.

In light of the results, clinical laboratories and anatomic pathology groups should expect that EGFR screening may soon become a companion diagnostic test as part of a precision medicine clinical guideline for early diagnosing of lung cancer.

—Stephen Beale

Related Information:

Overall Survival with Osimertinib in Resected EGFR-Mutated NSCLC

Study Shows Osimertinib Improves Survival Following Surgery for Non-Small Cell Lung Cancer

Lung Cancer Deaths Cut in Half with AstraZeneca Pill, Large Trial Finds

Adjuvant Osimertinib Improves Survival in Patients with Resected EGFR-Mutated NSCLC

AZD9291 Versus Placebo in Patients With Stage IB-IIIA Non-small Cell Lung Carcinoma, Following Complete Tumor Resection With or Without Adjuvant Chemotherapy. (ADAURA)

ADAURA Trial Results Provide New Hope for Patients with Early-Stage Non-Small Cell Lung Cancer

Updated Results from the ADAURA Trial: Continued Disease-Free Survival Benefit with Adjuvant Osimertinib vs Placebo in EGFR-Mutated Stage IB–IIIA NSCLC

Final ADAURA OS Analysis Reinforces Adjuvant Osimertinib as a Standard of Care for Patients with Stage IB to IIIA EGFR-Mutated Non–Small Cell Lung Cancer

NIH: Stage IIIA Non-Small Cell Lung Cancer

Lung Cancer Pill Cuts Risk of Death by Half, Says ‘Thrilling’ Study

Tagrisso Demonstrated Strong Overall Survival Benefit in the ADAURA Phase III Trial for Adjuvant Treatment of Patients with Early-Stage EGFR-Mutated Lung Cancer